Parallel Evaluation of Circulating Tumor DNA and Circulating Tumor Cells in Metastatic Colorectal Cancer

Liquid biopsy, encompassing circulating tumor (ctDNA) and circulating tumor cells, is under investigation to overcome spatial and temporal heterogeneity of metastatic colorectal cancer. Limited comparative data are available. In a cohort of 20 patients, we show that ctDNA was detectable in all cases, whereas circulating tumor cells were detectable in one-third of cases. ctDNA analysis appears readily available to be a candidate for clinical application in metastatic colorectal cancer. Background: Tissue biopsy is the gold standard for tumor genotyping, but it is an invasive procedure providing a single snapshot into tumor heterogeneity. Liquid biopsy approaches, encompassing the analysis of circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs), have been proposed as an alternative, with the potential of providing a comprehensive portrait of the tumor molecular landscape. In metastatic colorectal cancer (mCRC), both CTCs and ctDNA analysis have been investigated, but comparative analyses are limited. Methods: We collected blood samples from 20 consecutive patients with mCRC with at least 1 of the following inclusion criteria: high tumor burden (> 1 metastasis), intact colonic primary tumor, disease progression at the time of sampling, 2 cycles of cytotoxic chemotherapy of current treatment course, and time between last chemotherapy cycle 4 weeks. Results: Nineteen of 20 samples displayed the appropriate quality for CTC analysis. CTCs could be isolated in 7 (36.8%) of 19 evaluable patients. The median number of CTCs was 0 (range, 0-73). In 2 patients, we isolated > 1 CTC, and in five, we found 1 CTC. We retrieved ctDNA in all samples, with a median amount of 732,573 GE/mL (range, 174,774-174,078,615 GE/ mL). Concordance between ctDNA and tissue for RAS, BRAF, and ERBB2 alterations was found in 11 (84.6%) of 13 cases. Conclusions: In this cohort, we show that ctDNA was detectable in all cases, whereas CTCs were detectable in one-third of the cases. ctDNA analysis was achieved with a smaller amount of blood sampling and allowed molecular characterization. Our data indicate that ctDNA is a readily available candidate for clinical application in mCRC.